3-149213737-G-T

Variant names:

• chr3-149213737-G-T
• rs16861634
• NM_000096.4:c.147-1039C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000096.4(CP):​c.147-1039C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.093 in 151,962 control chromosomes in the GnomAD database, including 1,062 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.093 (1062 hom., cov: 32)
• Consequence: CP NM_000096.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.380
• Publications: 7 publications found

Genes affected

CP (HGNC:2295): (ceruloplasmin) The protein encoded by this gene is a metalloprotein that binds most of the copper in plasma and is involved in the peroxidation of Fe(II)transferrin to Fe(III) transferrin. Mutations in this gene cause aceruloplasminemia, which results in iron accumulation and tissue damage, and is associated with diabetes and neurologic abnormalities. Two transcript variants, one protein-coding and the other not protein-coding, have been found for this gene. [provided by RefSeq, Feb 2012]

CP Gene-Disease associations (from GenCC):

• aceruloplasminemia

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
• disorder of iron metabolism and transport

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CP	NM_000096.4	c.147-1039C>A		intron_variant	Intron 1 of 18	ENST00000264613.11	NP_000087.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CP	ENST00000264613.11	c.147-1039C>A		intron_variant	Intron 1 of 18	1	NM_000096.4	ENSP00000264613.6
CP	ENST00000490639.5	n.179-1039C>A		intron_variant	Intron 1 of 16	1
CP	ENST00000455472.3	c.267-1039C>A		intron_variant	Intron 2 of 3	5		ENSP00000426888.1
CP	ENST00000481169.5	n.147-1039C>A		intron_variant	Intron 1 of 17	2		ENSP00000418773.1

Frequencies

GnomAD3 genomes AF: 0.0930 AC: 14126 AN: 151844 Hom.: 1059 Cov.: 32

Gnomad AFR AF: 0.0215

Gnomad AMI AF: 0.0780

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.0611

Gnomad EAS AF: 0.379

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.0605

Gnomad NFE AF: 0.0929

Gnomad OTH AF: 0.0976

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0930 AC: 14134 AN: 151962 Hom.: 1062 Cov.: 32 AF XY: 0.0994 AC XY: 7383 AN XY: 74258

African (AFR) AF: 0.0215 AC: 893 AN: 41442

American (AMR) AF: 0.143 AC: 2182 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.0611 AC: 212 AN: 3468

East Asian (EAS) AF: 0.380 AC: 1963 AN: 5170

South Asian (SAS) AF: 0.147 AC: 707 AN: 4802

European-Finnish (FIN) AF: 0.149 AC: 1564 AN: 10528

Middle Eastern (MID) AF: 0.0616 AC: 18 AN: 292

European-Non Finnish (NFE) AF: 0.0929 AC: 6317 AN: 67986

Other (OTH) AF: 0.0980 AC: 207 AN: 2112

Alfa AF: 0.0638 Hom.: 91

Bravo AF: 0.0909

Asia WGS AF: 0.224 AC: 778 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.15
DANN	Benign	0.39
PhyloP100		-0.38
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs16861634; hg19: chr3-148931524;